title: Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation.
abstract: Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice (mrp1(+/+)) and MRP1-deficient mice (mrp1(-/-)) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in mrp1(-/-) mice compared with mrp1(+/+) mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed mrp1(-/-) mice were significantly lower than those from OVA-exposed mrp1(+/+) mice. Levels of OVA-specific IgE, IL-4, and IL-13 in BALF were also decreased in OVA-exposed mrp1(-/-) mice. IgE-mediated release of CysLTs from murine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role in the development of allergic airway inflammation through regulation of IgE-mediated CysLT export from mast cells.
authors.affiliation: Dept. of Respiratory Medicine, Juntendo Univ. School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. seigo@juntendo.ac.jp
authors.forename: Masakata
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Hironori
authors.initials: H
authors.lastname: Sagara
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Takahashi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Akio
authors.initials: A
authors.lastname: Mori
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.forename: Kazue
authors.initials: K
authors.lastname: Shimizu
authors.forename: Takenori
authors.initials: T
authors.lastname: Okada
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ota
authors.forename: Yoichi M
authors.initials: YM
authors.lastname: Ito
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagashima
authors.forename: Ryo
authors.initials: R
authors.lastname: Atsuta
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003545:Cysteine / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D003545:Cysteine; D007073:Immunoglobulin E; D015289:Leukotrienes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010047:Ovalbumin; C112381:cysteinyl-leukotriene; C421109:multidrug resistance-associated protein 1